The program involves studies of aging and senescence at the cellular level, with particular reference to the senescence and lifespan of human cell clones. The experimental material will be human diploid cells in culture, which are known to be spanned, and amoeba cells which can be given a lifespan. A major innovation will be the use of cell assembly techniques to detect changes in cell component function. Cell assembly, by bringing together nuclei, membranes and cytoplasmic components from various sources (including lifespanned and unspanned cells) will permit study of the way in which complex cellular subsystems interact, and facilitate detection of changes in subsystems (as opposed to molecular changes) with respect to time. Studies in relation to age will be (1) of antigens and enzymes, both total per cell and cytological distribution; (2) of cell behavior, including resistance to stress; (3) of the nature of the spanning factor which converts unspanned to spanned cells; (4) of the properties of cells assembled from components of both spanned and unspanned cells; (5) of the changes which take place in a diploid cell after infection with a virus which changes its lifespan. Techniques for assembling cells from components will be developed which involve a) assembly of components in artificial membranes; b) membrane fusion; c) improved instrumentation for microsurgery on tissue cells; d) improved techniques for following the behavior of large numbers of individual cells in culture. The experimental program will be backed up by a theoretical systems study of cells based on control loop processes, including cell clock and counting devices.